1. Antiviral Activity of Oral JNJ-53718678 in Healthy Adult Volunteers Challenged With Respiratory Syncytial Virus: A Placebo-Controlled Study.
- Author
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Stevens M, Rusch S, DeVincenzo J, Kim YI, Harrison L, Meals EA, Boyers A, Fok-Seang J, Huntjens D, Lounis N, Mari N K, Remmerie B, Roymans D, Koul A, and Verloes R
- Subjects
- Administration, Oral, Adolescent, Adult, Antiviral Agents pharmacology, Drug-Related Side Effects and Adverse Reactions epidemiology, Drug-Related Side Effects and Adverse Reactions pathology, Female, Healthy Volunteers, Humans, Imidazolidines pharmacology, Indoles pharmacology, Male, Middle Aged, Placebos administration & dosage, Respiratory Syncytial Virus Infections pathology, Respiratory Syncytial Virus Infections prevention & control, Respiratory Syncytial Virus, Human isolation & purification, Treatment Outcome, Viral Load, Virus Shedding, Young Adult, Antiviral Agents administration & dosage, Imidazolidines administration & dosage, Indoles administration & dosage, Respiratory Syncytial Virus Infections drug therapy, Respiratory Syncytial Virus, Human drug effects
- Abstract
Background: Respiratory syncytial virus (RSV) disease has no effective treatment. JNJ-53718678 is a fusion inhibitor with selective activity against RSV., Methods: After confirmation of RSV infection or 5 days after inoculation with RSV, participants (n = 69) were randomized to JNJ-53718678 75 mg (n = 15), 200 mg (n = 17), 500 mg (n = 18), or placebo (n = 17) orally once daily for 7 days. Antiviral effects were evaluated by assessing RSV RNA viral load (VL) area under the curve (AUC) from baseline (before the first dose) until discharge, time-to-peak VL, duration of viral shedding, clinical symptoms, and quantity of nasal secretions., Results: Mean VL AUC was lower for individuals treated with different doses of JNJ-53718678 versus placebo (203.8-253.8 vs 432.8 log10 PFUe.hour/mL). Also, mean peak VL, time to peak VL, duration of viral shedding, mean overall symptom score, and nasal secretion weight were lower in each JNJ-53718678-treated group versus placebo. No clear exposure-response relationship was observed. Three participants discontinued due to treatment-emergent adverse events of grade 2 and 1 electrocardiogram change (JNJ-53718678 75 mg and 200 mg, respectively) and grade 2 urticaria (placebo)., Conclusions: JNJ-53718678 at all 3 doses substantially reduced VL and clinical disease severity, thus establishing clinical proof of concept and the compound's potential as a novel RSV treatment., Clinical Trials Registration: ClinicalTrials.gov: NCT02387606; EudraCT number: 2014-005041-41.
- Published
- 2018
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